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Communications to the Editor |

Right Ventricular Dysfunction FREE TO VIEW

Dennis K. King, MD, FCCP
Author and Funding Information

Melbourne, FL

Correspondence to: Dennis K. King, MD, FCCP, Suite A, 1401 S Apollo Blvd, Melbourne, FL 32901; e-mail: dKingres@aol.com



Chest. 2005;127(4):1458-1459. doi:10.1378/chest.127.4.1458-a
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Published online

To the Editor:

In his article (April 2004)1concerning the impact of right ventricular (RV) dysfunction on the prognosis and therapy of normotensive patients with pulmonary embolism (PE), Dr. Kreit concludes, as have other recent reviewers,23 that thrombolytic therapy is not indicated for individuals who have echocardiographic evidence of RV dysfunction without hypotension or shock. Dr. Kreit may even have overestimated the mortality in this group of patients, as his Table 1 includes two studies45 in which there is no indication that hypotensive patients were excluded. When these studies are not considered, the average mortality falls from the quoted 9.3% for the four studies in the Table 1, to 4.5% for the remaining two studies. Additionally, Dr. Kreit does not comment on the 10-year retrospective study by Vieillard-Bbaron et al,6 in which 32 subjects with massive PE and echocardiographic RV dysfunction without frank shock had only a 3% mortality.

Dr. Kreit suggests that hypotensive patients have a higher mortality and quotes the 14% mortality in 43 such patients in a large registry.7However, in the study by Grifoni et al,8 included in Table 1, 19 patients were prospectively identified who had echocardiographic evidence of RV dysfunction and hypotension without shock. The mortality in this group was only 5%, identical to that in the normotensive patients in the study. Furthermore, in the study by Vieillard-Baron et al,6 in 32 patients with echocardiographic RV dysfunction and hypotension requiring vasopressor support but without metabolic acidosis, the mortality rate was 3% and no different than the in group without hypotension. In sharp contrast, 34 patients who were hypotensive with a metabolic acidosis despite intravascular volume expansion and vasopressor support had a 59% mortality rate. Although not randomized, it is notable that the mortality in these 34 patients was the same in the 14 patients receiving thrombolytics (57%) as in the 20 patients receiving only heparin (60%).

It is important to be fully aware of several limitations in the study by Jerjes-Sanchez et al,9 which Dr. Kreit cites, the only randomized prospective study to claim a survival advantage in patients in shock receiving thrombolytic and heparin therapy rather than heparin alone. The groups differed substantially with respect to the time from onset of symptoms of PE to onset of shock. The patients randomized to streptokinase presented quickly and directly to the study hospital, while those randomized to heparin were all transferred to the study hospital after sudden deterioration on heparin at another institution. This suggests a different pathophysiology between the groups, such as recurrent PE prior to randomization in the heparin only group.3 The patients in this study were very unusual. The patients were much younger than in most series of patients with PE (mean age, 51 years and 47 years in the two groups, respectively) and had extremely high estimated pulmonary artery systolic pressure (97 mm Hg and 94 mm Hg, respectively). Angina was reported in all patients, and three of the four patients who died and underwent autopsy all had grossly visible RV infarctions. Finally, the termination of the study after enrollment of only 8 of the intended 40 patients is problematic for two reasons. First, the small sample size lowers the confidence in the p value. That is, if a ninth patient had been enrolled and had a different outcome from the previous eight patients, the p value would be markedly higher. Second, the analysis of the data “as it accumulated” rather than at the intended end point of 40 patients requires the application of “sequential methods” to the statistical analysis in order for it to be valid10; it is far from clear that this was done.

It appears that what Dr. Dalan11 stated in an editorial in 2002 remains true today: “Despite > 3 decades of experience with thrombolytic agents, their role in the treatment of PE remains uncertain and controversial.” In making treatment decisions on individual patients with PE, however, the physician must bear in mind that the sharp rise in mortality from PE may not occur until patients are vasopressor dependent and exhibit a metabolic acidosis. Even in this latter group, solid evidence that thrombolytics confer a survival advantage is lacking.

Kreit, JW (2004) The impact of right ventricular dysfunction on the prognosis and therapy of normotensive patients with pulmonary embolism.Chest125,1539-1545
 
Stein, PD, Dalan, JE Thrombolytic therapy in acute pulmonary embolism. Dalan, JE eds.Venous thromboembolism.2003,253-270 Marcel Decker. New York, NY:
 
Arcasoy, SM, Vachani, A Local and systemic thrombolytic therapy for acute venous thromboembolism. Tapson, VF eds.Venous thromboembolism: clinical chest medicine.2003;Vol 24, No. 1,73-92 W. B. Saunders. Philadelphia, PA:
 
Kasper, W, Konstantinides, S, Geibel, A, et al Prognostic significance of right ventricular afterload stress detected by echocardiography in patients with clinically suspected pulmonary embolism.Heart1997;77,346-349
 
Ribeiro, A, Lindmarker, P, Juhlin-Dannfelt, A, et al Echocardiography Doppler in acute pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate.Am Heart J1997;134,479-487
 
Vieillard-Baron, A, Page, B, Augarde, R, et al Acute cor pulmonale in massive pulmonary embolism: incidence, echocardiographic pattern, clinical implications and recovery rate.Intensive Care Med2001;27,1481-1486
 
Goldhaber, SZ, Visani, L, DeRosa, M Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER).Lancet1999;353,1386-1389
 
Grifoni, S, Olivotto, I, Cecchini, P, et al Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction.Circulation2000;101,2817-2822
 
Jerjes-Sanchez, C, Ramirez-Rivera, A, deLourdes, GM, et al Streptokinase and heparin versus heparin alone in massive pulmonary embolism: a randomized controlled trial.J Thromb Thrombolysis1995;2,227-229
 
Civetta, JM, Colton, T How to read a medical article and understand basic statistics. Civetta, JM Taylor, RW Kirby, RR eds.Critical care. 3rd ed.1997,3-20 Lippincott-Raven Publishers. Philadelphia, PA:
 
Dalan, JE The uncertain role of thrombolytic therapy in the treatment of pulmonary embolism [editorial].Arch Intern Med2002;162,2521-2523
 

Figures

Tables

References

Kreit, JW (2004) The impact of right ventricular dysfunction on the prognosis and therapy of normotensive patients with pulmonary embolism.Chest125,1539-1545
 
Stein, PD, Dalan, JE Thrombolytic therapy in acute pulmonary embolism. Dalan, JE eds.Venous thromboembolism.2003,253-270 Marcel Decker. New York, NY:
 
Arcasoy, SM, Vachani, A Local and systemic thrombolytic therapy for acute venous thromboembolism. Tapson, VF eds.Venous thromboembolism: clinical chest medicine.2003;Vol 24, No. 1,73-92 W. B. Saunders. Philadelphia, PA:
 
Kasper, W, Konstantinides, S, Geibel, A, et al Prognostic significance of right ventricular afterload stress detected by echocardiography in patients with clinically suspected pulmonary embolism.Heart1997;77,346-349
 
Ribeiro, A, Lindmarker, P, Juhlin-Dannfelt, A, et al Echocardiography Doppler in acute pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate.Am Heart J1997;134,479-487
 
Vieillard-Baron, A, Page, B, Augarde, R, et al Acute cor pulmonale in massive pulmonary embolism: incidence, echocardiographic pattern, clinical implications and recovery rate.Intensive Care Med2001;27,1481-1486
 
Goldhaber, SZ, Visani, L, DeRosa, M Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER).Lancet1999;353,1386-1389
 
Grifoni, S, Olivotto, I, Cecchini, P, et al Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction.Circulation2000;101,2817-2822
 
Jerjes-Sanchez, C, Ramirez-Rivera, A, deLourdes, GM, et al Streptokinase and heparin versus heparin alone in massive pulmonary embolism: a randomized controlled trial.J Thromb Thrombolysis1995;2,227-229
 
Civetta, JM, Colton, T How to read a medical article and understand basic statistics. Civetta, JM Taylor, RW Kirby, RR eds.Critical care. 3rd ed.1997,3-20 Lippincott-Raven Publishers. Philadelphia, PA:
 
Dalan, JE The uncertain role of thrombolytic therapy in the treatment of pulmonary embolism [editorial].Arch Intern Med2002;162,2521-2523
 
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